Five cases of rhinocerebral mucormycosis (RCM) with different courses of illness and outcomes also due to different therapeutical strategies including Posaconazole as a new therapeutic option are described. Predisposing conditions for RCM are diabetes mellitus and immunosuppression. Diagnosis is often delayed because patients complain about nonspecific symptoms of acute rhinosinusitis, and initial CT imaging is unimpressive. Progressive disease, however, leads to early orbital and cerebral invasion. Due to the lack of typical clinical signs, diagnosis relies on histopathology. Therapy consists of the management of predisposing factors, radical surgical intervention and systemic antifungal therapy.We describe five cases of RCM with different comorbidities and outcomes.RCM remains a diagnostic and therapeutic challenge because it begins with nonspecific symptoms and ends as fulminant disease with high mortality. Here, systemic treatment with Posaconazole appears to be a more effective alternative to amphotericin.If a patient is suspected having RCM, improvement of predisposing diseases, radical surgical debridement and effective systemic antifungal therapy must be instituted immediately.